Altered structural connectome of children with auditory processing disorder: a diffusion MRI study.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional functional brain topology in children with APD. However, little is known about the structural organization in APD. We used diffusion MRI data to investigate the structural connectome of 58 children from 8 to 14 years old diagnosed with APD (n = 29) and children without hearing complaints (healthy controls, HC; n = 29). We investigated the rich-club organization and structural connection differences between groups. The APD group showed similar rich-club organization and edge-wise connection compared with the HC group. However, at the regional level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in the APD group. Only HCs demonstrated a positive association between APL and the listening-in-spatialized-noise-sentences task in the left orbital gyrus. In line with previous findings, the current results provide evidence for altered structural networks at the regional level in the APD group, suggesting the involvement of multimodal deficits and a role for structure-function alteration in the listening difficulties of children with APD.

Neural correlates of perceptual switching while listening to bistable auditory streaming stimuli.

Understanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a 700 ms silent response period after every third triplet were presented repeatedly, and human participants reported nearly equivalent proportions of 1- and 2-stream percepts. The pattern of behavioral responses was consistent with previous studies of visual and auditory bistable perception. The intermittent response paradigm has the benefit of evoking spontaneous perceptual switches that can be attributed to a well-defined stimulus event, enabling precise identification of the timing of perception-related neural events with event-related potentials (ERPs). Significantly more negative ERPs were observed for 2-streams compared to 1-stream, and for switches compared to non-switches during the sustained potential (500-1000 ms post-stimulus onset). Further analyses revealed that the negativity associated with switching was independent of switch direction, suggesting that spontaneous changes in perception have a unique neural signature separate from the observation that 2-stream percepts evoke more negative ERPs than 1-stream. Source analysis of the sustained potential showed activity associated with these differences originating in anterior superior temporal gyrus, indicating involvement of the ventral auditory pathway that is important for processing auditory objects.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

Cortical encoding of speech acoustics: Effects of noise and amplification.

OBJECTIVE: To investigate speech stimuli and background-noise-dependent changes in cortical auditory-evoked potentials (CAEPs) in unaided and aided conditions, and determine amplification effects on CAEPs. DESIGN: CAEPs to naturally produced syllables in quiet and in multi-talker babble were recorded, with and without a hearing aid in the right ear. At least 300 artifact-free trials for each participant were required to measure latencies and amplitudes of CAEPs. Acoustic characteristics of the hearing-aid-transduced stimuli were measured using in-the-canal probe microphone measurements to determine unaided versus aided SNR and to compare stimulus acoustic characteristics to CAEP findings. STUDY SAMPLE: Ten participants with normal hearing, aged 19 to 35 years. RESULTS: CAEP latencies and amplitudes showed significant effects of speech contrast, background noise, and amplification. N1 and P2 components varied differently across conditions. In general, cortical processing in noise was influenced by SNR and the spectrum of the speech stimuli. Hearing-aid-induced spectral and temporal changes to the speech stimuli affected P1-N1-P2 components. Amplification produced complex effects on latencies and amplitudes across speech stimuli and CAEP components, and for quiet versus noise conditions. CONCLUSION: CAEP components reflect spectral and temporal characteristics of speech stimuli and acoustic changes induced by background noise and amplification.

The co-adsorption of thymohydroquinone dimethyl ether (THQ) and coumarin present in the aqueous extract of Ayapana triplinervis on mild steel and its protection in hydrochloric acid up to 323 K: computational and physicochemical studies.

This study evaluates the corrosion inhibition property of the aqueous and alcoholic leaf extracts of the medicinal plant Ayapana triplinervis. The major components in the extracts are thymohydroquinone dimethyl ether (THQ) and coumarin. It is clear from the weight-loss studies that the water extract of the leaves (AYW) is superior to the alcoholic extract (AYA) in terms of offering corrosion inhibition. The 96% efficiency of 4% (v/v) AYW in 0.5 N HCl at room temperature changes to 84.62% at 323 K. The mixed-type inhibition behaviour of AYW shows slight dominance in the anodic direction. Studies suggest the multilayer adsorption of phytochemicals on the metal surface and that the adsorption follows the Temkin model. Theoretical studies using DFT and BIOVIA Materials Studio investigations establish THQ as a good inhibitor with high adsorption characteristics. Even though the concentration of coumarin in the extract is low, its presence in the extract facilitates the adsorption of THQ on the metal surface, which is evident from the MD simulation study. The changes in the surface topography and elemental composition of the metal specimen in the inhibited and uninhibited solution are monitored by SEM and EDX spectral studies. XPS data support the presence of both THQ and coumarin on the metal surface and the existence of co-ordinate bonding between the metal's d orbital and the O atoms of THQ. Theoretical and experimental studies support the mixed mode of adsorption of THQ as physisorption followed by chemisorption.

Effects of aging on neural processing during an active listening task.

Factors affecting successful listening in older adults and the corresponding electrophysiological signatures are not well understood. The present study investigated age-related differences in attention and temporal processing, as well as differences in the neural activity related to signal degradation during a number comparison task. Participants listened to digits presented in background babble and were tested at two levels of signal clarity, clear and degraded. Behavioral and electrophysiological measures were examined in 30 older and 20 younger neurologically-healthy adults. Relationships between performance on the number comparison task, behavioral measures, and neural activity were used to determine correlates of listening deficits associated with aging. While older participants showed poorer performance overall on all behavioral measures, their scores on the number comparison task were largely predicted (based on regression analyses) by their sensitivity to temporal fine structure cues. Compared to younger participants, older participants required higher signal-to-noise ratios (SNRs) to achieve equivalent performance on the number comparison task. With increasing listening demands, age-related changes were observed in neural processing represented by the early-N1 and later-P3 time windows. Source localization analyses revealed age differences in source activity for the degraded listening condition that was located in the left prefrontal cortex. In addition, this source activity negatively correlated with task performance in the older group. Together, these results suggest that older adults exhibit reallocation of processing resources to complete a demanding listening task. However, this effect was evident only for poorer performing older adults who showed greater posterior to anterior shift in P3 response amplitudes than older adults who were good performers and younger adults. These findings might reflect less efficient recruitment of neural resources that is associated with aging during effortful listening performance.

Altered brain network topology in children with auditory processing disorder: A resting-state multi-echo fMRI study.

Children with auditory processing disorder (APD) experience hearing difficulties, particularly in the presence of competing sounds, despite having normal audiograms. There is considerable debate on whether APD symptoms originate from bottom-up (e.g., auditory sensory processing) and/or top-down processing (e.g., cognitive, language, memory). A related issue is that little is known about whether functional brain network topology is altered in APD. Therefore, we used resting-state functional magnetic resonance imaging data to investigate the functional brain network organization of 57 children from 8 to 14 years old, diagnosed with APD (n = 28) and without hearing difficulties (healthy control, HC; n = 29). We applied complex network analysis using graph theory to assess the whole-brain integration and segregation of functional networks and brain hub architecture. Our results showed children with APD and HC have similar global network properties -i.e., an average of all brain regions- and modular organization. Still, the APD group showed different hub architecture in default mode-ventral attention, somatomotor and frontoparietal-dorsal attention modules. At the nodal level -i.e., single-brain regions-, we observed decreased participation coefficient (PC - a measure quantifying the diversity of between-network connectivity) in auditory cortical regions in APD, including bilateral superior temporal gyrus and left middle temporal gyrus. Beyond auditory regions, PC was also decreased in APD in bilateral posterior temporo-occipital cortices, left intraparietal sulcus, and right posterior insular cortex. Correlation analysis suggested a positive association between PC in the left parahippocampal gyrus and the listening-in-spatialized-noise -sentences task where APD children were engaged in auditory perception. In conclusion, our findings provide evidence of altered brain network organization in children with APD, specific to auditory networks, and shed new light on the neural systems underlying children's listening difficulties.

The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells.

Proteolysis-targeting chimeras (PROTACs) are a promising new class of drugs that selectively degrade cellular proteins of interest. PROTACs that target oncogene products are avidly being explored for cancer therapies, and several are currently in clinical trials. Drug resistance is a substantial challenge in clinical oncology, and resistance to PROTACs has been reported in several cancer cell models. Here, using proteomic analysis, we found intrinsic and acquired resistance mechanisms to PROTACs in cancer cell lines mediated by greater abundance or production of the drug efflux pump MDR1. PROTAC-resistant cells were resensitized to PROTACs by genetic ablation of ABCB1 (which encodes MDR1) or by coadministration of MDR1 inhibitors. In MDR1-overexpressing colorectal cancer cells, degraders targeting either the kinases MEK1/2 or the oncogenic mutant GTPase KRASG12C synergized with the dual epidermal growth factor receptor (EGFR/ErbB)/MDR1 inhibitor lapatinib. Moreover, compared with single-agent therapies, combining MEK1/2 degraders with lapatinib improved growth inhibition of MDR1-overexpressing KRAS-mutant colorectal cancer xenografts in mice. Together, our findings suggest that concurrent blockade of MDR1 will likely be required with PROTACs to achieve durable protein degradation and therapeutic response in cancer.

Intra-articular nodular fasciitis of the shoulder: a case report and review of the literature.

Nodular fasciitis is a benign proliferation of myofibroblasts usually arising adjacent to the fascia. In this report, we describe a rare case in which nodular fasciitis occurred in an intra-articular location in the shoulder of a 26-year-old man. The mass developed in the subscapularis recess of the shoulder and histological evaluation showed a myofibroblastic proliferation. MRI findings of intra-articular nodular fasciitis are discussed along with a review of previous reports.

Radiologic signs of weapons and munitions: How will noncombatants recognize them?

OBJECTIVE: The purpose of this work was to show the radiologic signs named after weapons and munitions along with their military counterparts to help radiologists recognize these signs, which will allow confident interpretation and diagnosis. CONCLUSION: Numerous pathologic conditions have classic radiologic manifestations that resemble weapons and ammunition. Most of these signs are highly memorable and easy to recognize. However, the names of the weapons (some of them antique and some not commonly known) may confuse radiologists who are not familiar with the appearance of such weapons as the scimitar, bayonet, or dagger. The value of the signs is reduced if the radiologist is unfamiliar with the appearance of the corresponding weapon.

Cortical Auditory-Evoked Potential and Behavioral Evidence for Differences in Auditory Processing between Good and Poor Readers.

BACKGROUND: The relationship between auditory processing (AP) and reading is thought to be significant; however our understanding of this relationship is somewhat limited. Previous studies have investigated the relation between certain electrophysiological and behavioral measures of AP and reading abilities in children. This study attempts to further understand that relation. PURPOSE: Differences in AP between good and poor readers were investigated using electrophysiological and behavioral measures. STUDY SAMPLE: Thirty-two children (15 female) aged 9-11 yr were placed in either a good reader group or poor reader group, based on the scores of a nationally normed reading test in New Zealand. RESEARCH DESIGN: Children were initially tested using an automated behavioral measuring system that runs through a tablet computer known as "Feather Squadron." Following the administration of Feather Squadron, cortical auditory-evoked potentials (CAEPs) were recorded using a speech stimulus (/m/) with the HEARLab® Cortical Auditory Evoked Potential Analyzer. DATA COLLECTION AND ANALYSIS: The children were evaluated on eight subsections of the Feather Squadron, and CAEP waveform peaks were visually identified and averaged. Separate Kruskal-Wallis analyses were performed for the behavioral and electrophysiological variables, with group (good versus poor readers) serving as the between-group independent variable and scores from the Feather Squadron AP tasks as well as CAEP latencies and amplitudes as dependent variables. After the children's AP status was determined, the entire group was further divided into three groups: typically developing, auditory processing disorder + reading difficulty (APD + RD), and RDs only. Statistical analyses were repeated for these subgroups. RESULTS: Poorer readers showed significantly worse scores than the good readers for the Tonal Pattern 1, Tonal Pattern 2, and Word Double Dichotic Right tasks. CAEP differences observed across groups indicated comorbid effects of RD and AP difficulties. N2 amplitude was significantly smaller for the poor readers. CONCLUSIONS: The current study found altered AP in poor readers using behavioral Feather Squadron measures and speech-evoked cortical potentials. These results provide further evidence that intact central auditory function is fundamental for reading development.

Impact of cognition and noise reduction on speech perception in adults with unilateral cochlear implants.

OBJECTIVES: The purpose of this study was to investigate the impact of cognition and noise reduction (NR) technology in cochlear implants (CIs) on speech perception and listening effort. METHODS: Thirteen adults fitted with unilateral CIs (Nucleus® 6, CP900) participated in this study. Participants performed: (I) cognitive tests of working memory and processing speed, (II) speech perception in noise tests, and (III) an auditory-visual dual-task paradigm to quantify listening effort, as a part of the three-phase experimental study. Both the participant and the tester, performing the outcome measures, were blinded to the NR settings (ON/OFF) of the CI for phases II and III. RESULTS: Speech intelligibility significantly improved with the NR activated, but was independent of individual differences in cognitive abilities. Listening effort did not significantly change with NR setting; however, there was a trend for participants with good working memory to have better speech perception scores with NR activated during the effortful listening task (dual-task paradigm). CONCLUSION: Future studies are warranted to explore the interaction between cognition and CI NR algorithms during an effortful listening task.